HIV remains a global health problem of unprecedented dimensions. Globally, there are about 35 Million people living with HIV, about 25 Million have died, and approximately 3.0 Million new HIV infections occur worldwide annually. In the US 60,000 new cases occur annually.
Human immunodeficiency virus (HIV-1) is a retrovirus that leads to AIDS, a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. HIV-1 enters macrophages and CD4+T cells by interaction of glycoproteins on its surface to receptors on the target cell followed by fusion of the viral envelope with the cell membrane and the release of the HIV capsid into the cell. HIV entry into human cells requires the interaction of several key proteins. It is initiated by binding of the HIV envelope surface glycoprotein subunit gp120 to the cellular receptor CD4, found on the surface of helper T cells in the human immune system, and a chemokine co-receptor, generally CCR5 or CXCR4, which is essential for HIV-1 infection. The binding of gp120 to CD4 causes a conformational change in gp120 allowing fusion of the membranes and subsequent entry of the viral core into the host cell. Thus blocking of the conformational change in gp41 that is crucial for fusion should inhibit viral entry into host cells.
Attempts to produce traditional vaccines have been unsuccessful. Although different non-traditional approaches to develop a vaccine are emerging, the prospect of generating a functional vaccine to control infection and spread of HIV is still many years away. Hence, there exists a need to create a therapeutic HIV vaccine to achieve long term remission without treatment or complete eradication of persistent virus and achievement of a full cure for HIV infection and AIDS.
Given the lack of efficacy of anti-HIV vaccines, and the lack of stability, bioavailability, low potency, toxicity problems, and the inability to kill the virus by the HIV-1 inhibitors developed so far, there is, accordingly, the need for developing novel compounds with a delivery system that is non-toxic, inert, water-soluble, stable, and biocompatible. Similarly, the compounds should be target specific, and have enhanced stability, higher potency, with minimal or no toxicity, and potentially capable to raise an immune response.